{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:44Z","timestamp":1787027804158,"version":"build-2736575974"},"reference-count":109,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011447","name":"Science and Technology, Department of Henan Province","doi-asserted-by":"publisher","award":["192102310350"],"award-info":[{"award-number":["192102310350"]}],"id":[{"id":"10.13039\/501100011447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011447","name":"Science and Technology, Department of Henan Province","doi-asserted-by":"publisher","award":["192102310379"],"award-info":[{"award-number":["192102310379"]}],"id":[{"id":"10.13039\/501100011447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still significant diagnostic and therapeutic challenges in the treatment of MPM. One of three main mesothelioma cell types, epithelioid mesothelioma makes up approximately 70% of all mesothelioma cases. Different observational findings are under process, but the molecular heterogeneity and pathogenesis of epithelioid malignant pleural mesothelioma (eMPM) are still not well understood. Through molecular analysis, expression profiling data were used to determine the possibility and optimal number of eMPM molecular subtypes. Next, clinicopathological characteristics and different molecular pathways of each subtype were analyzed to prospect the clinical applications and advanced mechanisms of eMPM. In this study, we identified two distinct epithelioid malignant pleural mesothelioma subtypes with distinct gene expression patterns. Subtype I eMPMs were involved in steroid hormone biosynthesis, porphyrin and chlorophyll metabolism, and drug metabolism, while subtype II eMPMs were involved in rational metabolism, tyrosine metabolism, and chemical carcinogenesis pathways. Additionally, we identified potential subtype-specific therapeutic targets, including CCNE1, EPHA3, RNF43, ROS1, and RSPO2 for subtype I and CDKN2A and RET for subtype II. Considering the need for potent diagnostic and therapeutic biomarkers for eMPM, we are anticipating that our findings will help both in exploring underlying mechanisms in the development of eMPM and in designing targeted therapy for eMPM.<\/jats:p>","DOI":"10.3390\/cells11182924","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T21:47:27Z","timestamp":1663624047000},"page":"2924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Define the Two Molecular Subtypes of Epithelioid Malignant Pleural Mesothelioma"],"prefix":"10.3390","volume":"11","author":[{"given":"Umair Ali Khan","family":"Saddozai","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6798-2991","authenticated-orcid":false,"given":"Saadullah","family":"Khattak","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8878-0675","authenticated-orcid":false,"given":"Muhammad Usman","family":"Akbar","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Badar","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4380-233X","authenticated-orcid":false,"given":"Nazeer Hussain","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6825-9690","authenticated-orcid":false,"given":"Longxiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6645-5786","authenticated-orcid":false,"given":"Xiangqian","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Institute of Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1177\/107327480601300402","article-title":"Malignant pleural mesothelioma: A comprehensive review","volume":"13","author":"Robinson","year":"2006","journal-title":"Cancer Control."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e401","DOI":"10.1016\/j.clgc.2015.05.009","article-title":"Malignant Mesothelioma of the Tunica Vaginalis: A Rare Neoplasm\u2014Case Report and Literature Review","volume":"13","year":"2015","journal-title":"Clin. 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